Water safety plans and climate change mitigation

[Excerpt] Definition Quality water at affordable prices for all is a key condition for the promotion of public health, environmental sustainability, and quality and safety of life. In a context of growing external uncertainties arising from changes in the climate and the environment, ensuring these conditions is an upward concern and is of utmost relevance to increase scientific research on the impacts of climate change on water quality modification and in minimization/mitigation strategies

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

VEGF is upregulated by hypoxia-induced mitogenic factor via the PI-3K/Akt-NF-κB signaling pathway

BACKGROUND: Hypoxia-induced mitogenic factor (HIMF) is developmentally regulated and plays an important role in lung pathogenesis. We initially found that HIMF promotes vascular tubule formation in a matrigel plug model. In this study, we investigated the mechanisms which HIMF enhances expression of vascular endothelial growth factor (VEGF) in lung tissues and epithelial cells. METHODS: Recombinant HIMF protein was intratracheally instilled into adult mouse lungs, VEGF expression was examined by immunohistochemical staining and Western blot. The promoter-luciferase reporter assay, RT-PCR, and Western blot were performed to examine the effects of HIMF on VEGF expression in mouse lung epithelial cell line MLE-12. The activation of NF-kappa B (NF-κB) and phosphorylation of Akt, IKK and IκBα were examined by luciferase assay and Western blot, respectively. RESULTS: Intratracheal instillation of HIMF protein resulted in significant increase of VEGF, mainly localized to airway epithelial and alveolar type II cells. Deletion of NF-κB binding sites within VEGF promoter abolished HIMF-induced VEGF expression in MLE-12 cells, suggesting that activation of NF-κB is essential for VEGF upregulation induced by HIMF. Stimulation of lung epithelial cells by HIMF resulted in phosphorylation of IKK and IκBα, leading to activation of NF-κB. In addition, HIMF strongly induced Akt phosphorylation, and suppression of Akt activation by specific inhibitors and dominant negative mutants for PI-3K, and IKK or IκBα blocked HIMF-induced NF-κB activation and attenuated HIMF-induced VEGF production. CONCLUSION: These results suggest that HIMF enhances VEGF production in mouse lung epithelial cells in a PI-3K/Akt-NF-κB signaling pathway-dependent manner, and may play critical roles in pulmonary angiogenesis

Concomitant ablation of atrial fibrillation in octogenarians: an observational study

<p>Abstract</p> <p>Background</p> <p>Cardiac surgery is increasingly required in octogenarians. These patients frequently present atrial fibrillation (AF), a significant factor for stroke and premature death. During the last decade, AF ablation has become an effective procedure in cardiac surgery. Because the results of concomitant AF ablation in octogenarians undergoing cardiac surgery are still not clear, we evaluated the outcome in these patients.</p> <p>Methods</p> <p>Among 200 patients undergoing concomitant AF ablation (87% persistent AF), 28 patients were ≥ 80 years (82 ± 2.4 years). The outcome was analysed by prospective follow up after 3, 6, 12 months and annually thereafter. Freedom from AF was calculated according to the Kaplan-Meier method.</p> <p>Results</p> <p>Octogenarians were similar to controls regarding AF duration (48 ± 63.2 versus 63 ± 86.3 months, n.s.) and left atrial diameter (49 ± 6.1 versus 49 ± 8.8 mm, n.s.), but differed in EuroSCORE (17.3 ± 10.93 versus 7.4 ± 7.31%, p < 0.001), prevalence of paroxysmal AF (25.0 versus 11.0%, p = 0.042) and aortic valve disease (67.8 versus 28.5%, p < 0.001). ICU stay (8 ± 16.9 versus 4 ± 7.2 days, p = 0.027), hospital stay (20 ± 23.9 versus 14 ± 30.8 days, p < 0.05), and 30-d-mortality (14.3 versus 4.6%, p = 0.046) were increased. After 12 ± 6.1 months of follow-up (95% complete), 14 octogenarians (82%) and 101 controls (68%, n.s.) were in sinus rhythm; 59% without antiarrhythmic drugs in either group (n.s.). Sinus rhythm restoration was associated with improved NYHA functional class and renormalization of left atrial size. Cumulative freedom from AF demonstrated no difference between groups. Late mortality was higher in octogenarians (16.7 versus 6.1%, p = 0.065).</p> <p>Conclusion</p> <p>Sinus rhythm restoration rate and functional improvement are satisfactory in octogenarians undergoing concomitant AF ablation. Hence, despite an increased perioperative risk, this procedure should be considered even in advanced age.</p

“No-one would sleep if we didn’t have books!”: Understanding shared reading as family practice and family display

Families are pivotal in terms of facilitating children’s language development, including their ability to read. However, to date, there is little research designed to understand how shared reading operates within the realm of everyday family practices. Drawing on data from a study which set out to explore shared reading practices in the home, this article considers reading within the context of the family and everyday family life. In-depth interviews were carried out with 29 parents of pre-school children to investigate shared reading practices within a socially and culturally mixed sample. This study revealed that the relationship between shared reading practices and family practices is recursive. In particular, building on the seminal work of Finch reading was seen to be a specific feature of family practice and routine, and acts as a form of family display. Furthermore, this article demonstrates how shared reading contributes toward the ways in which structure and agency may operate in a family setting. Constructing reading as a family practice and a form of display makes an important contribution to understandings of home literacy practices and behaviors. This article concludes that endeavors to engage families with shared reading therefore require a comprehensive understanding of family life and family practices and the role of shared reading within

Circadian Clock Gene Expression in the Coral Favia fragum over Diel and Lunar Reproductive Cycles

Natural light cycles synchronize behavioral and physiological cycles over varying time periods in both plants and animals. Many scleractinian corals exhibit diel cycles of polyp expansion and contraction entrained by diel sunlight patterns, and monthly cycles of spawning or planulation that correspond to lunar moonlight cycles. The molecular mechanisms for regulating such cycles are poorly understood. In this study, we identified four molecular clock genes (cry1, cry2, clock and cycle) in the scleractinian coral, Favia fragum, and investigated patterns of gene expression hypothesized to be involved in the corals' diel polyp behavior and lunar reproductive cycles. Using quantitative PCR, we measured fluctuations in expression of these clock genes over both diel and monthly spawning timeframes. Additionally, we assayed gene expression and polyp expansion-contraction behavior in experimental corals in normal light:dark (control) or constant dark treatments. Well-defined and reproducible diel patterns in cry1, cry2, and clock expression were observed in both field-collected and the experimental colonies maintained under control light:dark conditions, but no pattern was observed for cycle. Colonies in the control light:dark treatment also displayed diel rhythms of tentacle expansion and contraction. Experimental colonies in the constant dark treatment lost diel patterns in cry1, cry2, and clock expression and displayed a diminished and less synchronous pattern of tentacle expansion and contraction. We observed no pattern in cry1, cry2, clock, or cycle expression correlated with monthly spawning events suggesting these genes are not involved in the entrainment of reproductive cycles to lunar light cycles in F. fragum. Our results suggest a molecular clock mechanism, potentially similar to that in described in fruit flies, exists within F. fragum

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Proximity of Transmembrane Segments 5 and 8 of the Glutamate Transporter GLT-1 Inferred from Paired Cysteine Mutagenesis

BACKGROUND: GLT-1 is a glial glutamate transporter which maintains low synaptic concentrations of the excitatory neurotransmitter enabling efficient synaptic transmission. Based on the crystal structure of the bacterial homologue Glt(Ph), it has been proposed that the reentrant loop HP2, which connects transmembrane domains (TM) 7 and 8, moves to open and close access to the binding pocket from the extracellular medium. However the conformation change between TM5 and TM8 during the transport cycle is not clear yet. We used paired cysteine mutagenesis in conjunction with treatments with Copper(II)(1,10-Phenanthroline)(3) (CuPh), to verify the predicted proximity of residues located at these structural elements of GLT-1. METHODOLOGY/PRINCIPAL FINDINGS: To assess the proximity of transmembrane domain (TM) 5 relative to TM8 during transport by the glial glutamate transporter GLT-1/EAAT2, cysteine pairs were introduced at the extracellular ends of these structural elements. A complete inhibition of transport by Copper(II)(1,10-Phenanthroline)(3) is observed in the double mutants I295C/I463C and G297C/I463C, but not in the corresponding single mutants. Glutamate and potassium, both expected to increase the proportion of inward-facing transporters, significantly protected against the inhibition of transport activity of I295C/I463C and G297C/I463C by CuPh. Transport by the double mutants I295C/I463C and G297C/I463C also was inhibited by Cd(2+). CONCLUSIONS/SIGNIFICANCE: Our results suggest that TM5 (Ile-295, Gly-297) is in close proximity to TM8 (Ile-463) in the mammalian transporter, and that the spatial relationship between these domains is altered during the transport cycle

Prefrontal dopamine and the dynamic control of human long-term memory

Dopaminergic projections to the prefrontal cortex support higher-order cognitive functions, and are critically involved in many psychiatric disorders that involve memory deficits, including schizophrenia. The role of prefrontal dopamine in long-term memory, however, is still unclear. We used an imaging genetics approach to examine the hypothesis that dopamine availability in the prefrontal cortex selectively affects the ability to suppress interfering memories. Human participants were scanned via functional magnetic resonance imaging while practicing retrieval of previously studied target information in the face of interference from previously studied non-target information. This retrieval practice (RP) rendered the non-target information less retrievable on a later final test—a phenomenon known as retrieval-induced forgetting (RIF). In total, 54 participants were genotyped for the catechol-O-methyltransferase (COMT) Val108/158Met polymorphism. The COMT Val108/158Met genotype showed a selective and linear gene-dose effect on RIF, with the Met allele, which leads to higher prefrontal dopamine availability, being associated with greater RIF. Mirroring the behavioral pattern, the functional magnetic resonance imaging data revealed that Met allele carriers, compared with Val allele carriers, showed a greater response reduction in inhibitory control areas of the right inferior frontal cortex during RP, suggesting that they more efficiently reduced interference. These data support the hypothesis that the cortical dopaminergic system is centrally involved in the dynamic control of human long-term memory, supporting efficient remembering via the adaptive suppression of interfering memories